Venous thromboembolic disease (VTE) is associated with more than 300,000 hospitalizations and results in thousands of deaths annually. Despite the magnitude of the problem, optimal management of patients experiencing first deep vein thrombosis is unclear. Current treatment includes short-term full dose oral antithrombotic therapy with warfarin. Unfortunately, this treatment is associated with a very high rate of recurrence once therapy is stopped. In addition, poor compliance secondary to frequent laboratory monitoring and bleeding complications limit this treatment regimen's overall effectiveness. Presently, there is no clinical regimen which has been proven to have an acceptable risk/benefit ratio to support long-term prophylaxis. This appears true for high risk patients (factor V Leiden mutation) as well as for the general population. The primary aim of this proposal is to assess the net benefit of 3 to 4 years of low-dose warfarin (1.5-2.0) in the secondary prevention of idiopathic venous thromboembolism. The proposal is designed to evaluate patients with and without factor V Leiden. The proposed trial is a randomized double-blind, placebo-controlled trial of 3 to 4 years of anticoagulant therapy with low-dose warfarin prevention of recurrent deep vein thrombosis. The study will enroll 800 patients. Enrollment is designed to ensure participation of 300 patients with factor V Leiden. Patients will be enrolled from 25 clinical sites. Men and women of 40 years with documented idiopathic VTE who have finished standard therapy will be randomized to usual care plus placebo or usual care plus a 3- year regimen of low-dose warfarin. Following titration, the protocol will require infrequent laboratory monitoring. Trial endpoints include recurrent venous thrombosis, major bleeding, and all cause mortality for the group as a whole or factor V Leiden mutation subgroup. Events will be assessed by yearly visits and bi-monthly questionnaires at the time of the INR monitoring.